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Biomedical subjects

M Terashima

Publications and source records attributed to M Terashima.

At least 37 records · Page 2Linked to original sources
PubMed2001

Arginine-specific ADP-ribosyltransferase on the surface of gizzard smooth muscle cells and the involvement of phosphatidylinositol 3-kinase in maintaining the activity of this transferase.

An arginine-specific ADP-ribosyltransferase activity was detected in chicken gizzard smooth muscle, and the specific activity is highest in the membrane fraction. This transferase is released from the membrane fraction by phosphatidylinositol-specific phospholipase C (PI-PLC), suggesting that it is a glycosylphosphatidylinositol (GPI)-anchored protein. When primary cultured gizzard smooth muscle cells (SMCs) were incubated with [adenylate-(32)P]NAD, several proteins were labeled. The labeling was inhibited by preincubation of the cells with PI-PLC, or by the addition of L-arginine to the reaction, and was sensitive to hydroxylamine treatment. The activity of the transferase was maintained in differentiated SMCs cultured with insulin, but was dramatically decreased concomitantly with cell dedifferentiation induced by serum or a specific PI3-kinase inhibitor, LY294002. These results indicate that the GPI-anchored arginine-specific ADP-ribosyltransferase is expressed on the surface of differentiated SMCs and can modify several cell surface proteins. Our results also suggest that PI3-kinase is involved in the regulation of transferase activity during differentiation.

ADP Ribose Transferases↗
PubMed2001

Improved reproducibility of intravascular ultrasound assessment of coronary in-stent neointima with the use of an echogenic contrast agent.

The present study evaluated a new technique that has the potential to improve the border detection of in-stent neointima using an echogenic contrast agent during intravascular ultrasound (IVUS). To confirm the reproducibility of IVUS imaging for measuring the cross-sectional in-stent neointima area, inter- and intra-observer variability and correlation were determined. Conventional IVUS (plain IVUS) and IVUS using a contrast agent (contrast IVUS) were performed in 24 subjects 6.5+/-1.5 months after undergoing a Palmaz-Schatz coronary stent implant. Conventional IVUS delineated completely the in-stent neointima in 6 subjects (25%). In the remaining 18 subjects (75%), delineation of the neointima was incomplete despite the use of various combinations of imaging conditions (eg, transmission, compress, post-process). With contrast IVUS, the boundary of the neointima, and therefore the neointima area, was clearly distinguishable, and this resulted in complete delineation of the neointima in all 24 subjects. With a contrast agent, inter- and intra-observer variability significantly decreased (0.94+/-0.69mm2 conventional IVUS vs 0.37+/-0.40mm2 contrast IVUS, p<0.001; 0.69+/-0.56mm2 conventional IVUS vs 0.07+/-0.10mm2 contrast IVUS, p<0.0001; respectively). Thus, contrast IVUS provides a reproducible method for the quantitative analysis of in-stent neointima with excellent inter- and intra-observer correlation.

Aged↗
PubMed2001

[Novel biodegradable materials for drug delivery systems (DDS)].

The authors provide three new and different types of fibrin gels (FCs) and a chitosan sheet (BC) using an ultraviolet (UV)-crosslinking method. They are 1) FC-UV, 2) gelatin entrapped FC; FC (Gp)-UV, 3) chitosan entrapped FC; FC (Cs)-UV and 4) BC-UV. Each material was loaded with aqueous cis-platinum (CDDP), and both the degradation of the drug carriers and the release profile of the CDDP were examined in vitro. The FCs, 1)-3), gradually degraded and dissolved within 10-12 days. The BC, 4), maintained its original weight for more than 30 days. Each FC showed a sustained release of CDDP for 10 days, while BC provided an initial bursting of the loaded drug. New materials 2) and 3) show great potential as drug carriers for DDS and further in vivo studies are now proceeding.

Biodegradation, Environmental↗
PubMed2000

Cystatin C and cathepsin B in CSF from patients with inflammatory neurologic diseases.

BACKGROUND: In CSF, proteolytic enzymes are believed to have crucial roles in the initiation and progression of inflammatory neurologic diseases (IND). Cystatin C, a major cysteine protease inhibitor in CSF, is tightly bound to cathepsin B and H. OBJECTIVE: To determine if cystatin C is involved in the disease process of IND, the authors measured the cystatin C concentration by ELISA method and cathepsin B and H activities in the CSF of patients with acute IND. METHODS: Cystatin C concentration and cathepsin B and H activities were measured in CSF samples taken from patients during the acute phase of their disease. Subjects studied were 8 patients with Guillain-Barré syndrome (GBS), 5 with chronic inflammatory demyelinating polyneuropathy (CIDP), 12 with MS, 16 with aseptic meningitis, 15 with neurodegenerative diseases as disease controls, and 35 healthy controls. RESULTS: A significant decrease in CSF cystatin C level was seen in the patients with GBS, CIDP, and MS compared to the control subjects. High cathepsin B activity, but not cathepsin H activity, was also observed in the patients with GBS, CIDP, and MS. CONCLUSION: Cystatin C levels in CSF measured by ELISA may help the physician recognize GBS, CIDP, and MS. Decreased levels of cystatin C may be related to the high levels of cathepsin B activity seen in the CSF of patients with GBS, CIDP, and MS.

Adult↗
PubMed2000

Effects of sugar concentration on recombinant human alpha(1)-antitrypsin production by genetically engineered rice cell.

Productivity of recombinant human alpha(1)-antitrypsin (rAAT) with a genetically engineered rice cell using an inducible promoter has been studied by batch-wise and continuous production. A simple model explained the effect of proteases released from the disrupted cells on the rAAT degradation. Glucose concentration in the medium significantly affected the rAAT productivity in the continuous production, because the rAAT was induced by sugar depletion. When the fresh medium containing 5mM glucose was supplied to the continuous bioreactor, induction time was long and the productivity was low, indicating that the glucose concentration in the cells was high enough as to repress the promoter. When the glucose concentration in the fresh medium was reduced to 0.5mM, total amount of rAAT produced in 70h cultivation reached 6.7-7.6mg/g-dry cell, which was two times larger than the control medium without glucose.

Journal Article↗
PubMed2000

Phorbol ester synergistically increases interferon regulatory factor-1 and inducible nitric oxide synthase induction in interferon-gamma-treated RAW 264.7 cells.

The roles of PKC in iNOS induction by IFN-gamma have been shown in some cell types. The effect of a PKC activator, phorbol ester, in iNOS induction is thought to be due to multiple mechanisms, and it is necessary to examine the involvement of phorbol ester on IFN-gamma-induced iNOS in detail. In the present study, we investigated the mechanisms of phorbol ester on IFN-gamma-induced iNOS in RAW 264.7 cells. PMA synergistically increased iNOS activity, protein and mRNA levels in IFN-gamma-treated RAW 264.7 cells. PMA together with IFN-gamma increased iNOS mRNA without affecting the iNOS mRNA degradation, suggesting that the synergistic effect of PMA on IFN-gamma-induced iNOS mRNA production may depend on the elevation of the transcription rate rather than a prolongation of mRNA stability. The DNA binding proteins that are involved in the regulation of iNOS expression are mainly NF-kappa B and IRF-1. IRF-1 transcriptionally regulates many IFN-inducible genes such as iNOS whose promoter contains an IRF-1 binding site. PMA might modulate iNOS induction as a cosignal with IFN-gamma in RAW 264.7 cells because the synergistic effect of PMA was mediated through IRF-1, rather than NF-kappa B. Ro 31-8220, a PKC inhibitor, decreased iNOS activity, protein, mRNA levels and IRF-1 activity, indicating that the effect of PMA on iNOS induction might occur via the PKC pathway. It is evidence that PKC plays an important role in IRF-1 activation and that phorbol ester has a synergistic effect on iNOS induction through IRF-1 activation in IFN-gamma-treated RAW 264.7 cells. The synergistic effect of PMA on IFN-gamma-induced IRF-1 binding activity was observed in macrophage cell line J774 cells as well as RAW 264.7 cells, but not in thioglycollate-elicited peritoneal macrophages.

Animals↗
PubMed2000

Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation.

CD26 is a T cell activation antigen known to bind adenosine deaminase and have dipeptidyl peptidase IV activity. Cross-linking of CD26 and CD3 with immobilized mAbs can deliver a costimulatory signal that contributes to T cell activation. Our earlier studies revealed that cross-linking of CD26 induces its internalization, the phosphorylation of a number of proteins involved in the signaling pathway, and subsequent T cell proliferation. Although these findings suggest the importance of internalization in the function of CD26, CD26 has only 6 aa residues in its cytoplasmic region with no known motif for endocytosis. In the present study, we have identified the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIR) as a binding protein for CD26 and that mannose 6-phosphate (M6P) residues in the carbohydrate moiety of CD26 are critical for this binding. Activation of peripheral blood T cells results in the mannose 6 phosphorylation of CD26. In addition, the cross-linking of CD26 with an anti-CD26 antibody induces not only capping and internalization of CD26 but also colocalization of CD26 with M6P/IGFIIR. Finally, both internalization of CD26 and the T cell proliferative response induced by CD26-mediated costimulation were inhibited by the addition of M6P, but not by glucose 6-phosphate or mannose 1-phosphate. These results indicate that internalization of CD26 after cross-linking is mediated in part by M6P/IGFIIR and that the interaction between mannose 6-phosphorylated CD26 and M6P/IGFIIR may play an important role in CD26-mediated T cell costimulatory signaling.

Carbohydrate Metabolism↗
PubMed2000

E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas.

BACKGROUND: E (epithelial)-cadherin, the cell adhesion molecule also considered a potential invasion/metastasis suppressor, is mutationally inactivated in nearly half of all undifferentiated-scattered (diffuse-type) gastric carcinomas. In addition, silencing of E-cadherin by CpG methylation within its promoter region has been reported in several gastric carcinoma cell lines. We investigated the methylation status of the E-cadherin promoter region in 53 primary human gastric carcinomas. METHODS: Hypermethylation of the E-cadherin promoter was determined by utilizing methylation-specific polymerase chain reaction (PCR)-single-strand conformation polymorphism (MSP-SSCP) analysis followed by direct sequencing of PCR products. Expression of E-cadherin was studied by western blot analysis. All statistical tests were two-sided. RESULTS: Hypermethylation of the E-cadherin promoter was evident in 27 (51%) of 53 primary gastric carcinomas examined by MSP-SSCP. It occurred more frequently in carcinomas of the undifferentiated-scattered type (in 15 [83%] of 18) than in other histologic subtypes (in 12 [34%] of 35) (P =.0011, Fisher's exact test), and it was present at similar rates in early (in six [60%] of 10) versus advanced (in 21 [49%] of 43) carcinomas (P =.73, Fisher's exact test). Methylation occurring at all cytosine-guanosine sequences (CpGs) near the transcriptional start site was confirmed in six of six tumors examined by bisulfite-DNA sequencing, including two early gastric carcinomas. In addition, loss or diminished expression of E-cadherin was confirmed by western blotting in four of the six tumor tissues demonstrating hypermethylation. CONCLUSIONS: The E-cadherin promoter frequently undergoes hypermethylation in human gastric cancers, particularly those of the undifferentiated-scattered histologic subtype. E-cadherin promoter hypermethylation is associated with decreased expression and may occur early in gastric carcinogenesis.

Blotting, Western↗
PubMed2000

Response of the radial artery to three vasodilatory agents.

We examined the response of the radial artery to vasoactive agents (isosorbide dinitrate, ISDN, 1 mg, 3 mg, and 5 mg; verapamil, 1 mg, 3 mg, and 5 mg; and lidocaine, 10 mg, 30 mg, and 50 mg) in 100 consecutive patients admitted for elective coronary angiography. The drug solutions were directly injected into the radial artery from the puncture site. As a result, 5 mg of ISDN increased the diameter of the radial artery by 31% and 28.8% at the proximal and distal sites, respectively. Similarly, 5 mg of verapamil increased it by 9% and 10.8% at the proximal and distal site, respectively. But 10 mg of lidocaine decreased it by -15.6% and -12.1% at the proximal and distal site, respectively. At the doses utilized, ISDN was the most potent vasodilator for the radial artery and lidocaine caused paradoxical vasoconstriction.

Adult↗
PubMed2000

Surgical results for centrally-located early stage lung cancer.

BACKGROUND: With the increasing use of mass screening programs for lung cancer, and especially the use of sputum cytology, the incidence of roentgenographically occult lung cancer has been increasing. These occult cancers comprise mainly histologically centrally-located early stage lung cancers. This study examined the clinicopathologic characteristics and surgical results of centrally-located early stage lung cancer. RESULTS: From 1980 to 1998, there were 98 patients and 99 lesions of centrally-located early stage lung cancer resected. A total of 64 patients were detected by mass screening. Histologic examination revealed that 96 lesions were squamous cell carcinoma, and in these patients, there were 10 lesions of carcinoma in situ. The 5-year survival rate was 81.4% in all patients, and 88.9% in carcinoma in situ patients. In the postoperative follow-up period, a second lung cancer occurred in 13 patients. CONCLUSIONS: The surgical results for centrally-located early lung cancer were good. However, sometimes these cancers are accompanied by a second centrally-located primary lung cancer, so it is necessary to follow-up with sputum cytology to allow early detection of additional centrally-located lung cancer.

Adenocarcinoma↗
PubMed2000

Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome.

OBJECTIVES: To determine the morphologic features of coronary plaques associated with acute coronary syndrome, we prospectively followed patients with atherosclerotic disease identified by intravascular ultrasound (IVUS). BACKGROUND: Although clinical evaluation of the vulnerable atherosclerotic plaque is important, few data exist regarding the morphology of the vulnerable plaque in clinical settings. METHODS: We examined 114 coronary sites without significant stenosis by angiography (<50% diameter stenosis) in 106 patients. All the sites exhibited atherosclerotic lesions by IVUS. These lesions consisted of 22 concentric and 92 eccentric plaques with a percent plaque area averaging 59 +/- 12%. RESULTS: During the follow-up period of 21.8 +/- 6.4 months (range 1 to 24), 12 patients had an acute coronary event at a previously examined coronary site at an average of 4.0 +/- 3.4 months after the initial IVUS study. All the preexisting plaques related to the acute events exhibited an eccentric pattern and the mean percent plaque area was 67 +/- 9%, which was greater than plaque area in the other 90 patients without acute events (57 +/- 12%, p < 0.05). There was no statistically significant difference in lumen area between two patient groups (6.7 +/- 3.0 vs. 7.5 +/- 3.7 mm2). Among 12 coronary sites with an acute occlusion, 10 sites contained the echolucent zones, eight of these shallow and two deep, likely representing a lipid-rich core. In 90 sites without acute events, an echolucent zone in the shallow portion was seen at only four sites (p < 0.05). CONCLUSIONS: Large eccentric plaque containing an echolucent zone by IVUS can be at increased risk for instability even though the lumen area is preserved at the time of initial study. Compensatory enlargement of vessel wall due to remodeling may contribute to the relatively small degree of stenosis by angiography.

Angina Pectoris↗
PubMed2000

Preparation and dynamic viscoelasticity characterization of alkali-solubilized collagen from shark skin.

Alkali-solubilized collagens, prepared by alkali-acid extraction and alkali direct extraction (abbreviated AASC and ALSC, respectively), were characterized by dynamic viscoelastic measurement of collagen solution (10 mg/mL). The optimum preparative conditions in terms of yield and polypeptide size are as follows: for the alkali-acid extraction, a pretreatment with 0.5 or 1 M NaOH containing 15% Na(2)SO(4) within 5 days at 20 degrees C followed by the subsequent acid extraction, and for the alkaline direct extraction, a treatment with 0.5 M NaOH containing 10% NaCl at 4 degrees C for 20-30 days. A major portion of the polypeptide sizes of AASC and ALSC is composed of alpha chains (alpha1 and alpha2). Dynamic viscoelasticity of collagen solution was measured as a function of temperature. AASC showed a greater contribution of elastic behavior rather than viscous behavior. On the contrary, ALSC exhibits a stronger viscous behavior than elastic behavior.

Animals↗
PubMed2000

Physical properties of shark gelatin compared with pig gelatin.

Physical properties of shark gelatin were examined during gel formation and postgelation in comparison with pig gelatin. Samples with various concentrations and pH values were evaluated by breaking strength, dynamic viscoelasticity, and dynamic light scattering. Sol-gel and gel-sol transition temperatures for shark gelatin were remarkably lower than those for pig gelatin. Shark gelatin gel shows a narrower pH range to form a stable gel compared with pig gelatin. Melting enthalpy of shark gelatin gel was greater than that of pig gelatin gel, and G' of shark gelatin gel changed more extensively with rising temperature in comparison with pig gelatin gel. It is concluded that shark gelatin has different characteristics from pig gelatin not only for gel characteristics but also for the solution property.

Animals↗
PubMed2000

Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease.

OBJECTIVE: Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting. METHODS: We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound. RESULTS: FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant). CONCLUSION: These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.

Adrenergic beta-Antagonists↗
PubMed2000

Mouse T-cell antigen rt6.1 has thiol-dependent NAD glycohydrolase activity.

Mouse Rt6.1 and Rt6.2, homologues of rat T-cell RT6 antigens, catalyze arginine-specific ADP-ribosylation. Without an added ADP-ribose acceptor, Rt6.2 shows NAD glycohydrolase (NADase) activity. However, Rt6.1 has been reported to be primarily an ADP-ribosyltransferase, but not an NADase. In the present study, we obtained evidence that recombinant Rt6.1 catalyzes NAD glycohydrolysis but only in the presence of DTT. The NADase activity of Rt6.1 observed in the presence of DTT was completely inhibited by N-ethylmaleimide (NEM). Native Rt6.1 antigen, immunoprecipitated from BALB/c mouse splenocytes with polyclonal antibodies generated against recombinant RT6.1, also exhibited NADase activity in the presence of DTT. Compared with Rt6.2, Rt6.1 has two extra cysteine residues at positions 80 and 201. When Cys-80 and Cys-201 in Rt6.1 were replaced with the corresponding residues of Rt6.2, serine and phenylalanine, respectively, Rt6.1 catalyzed the NADase reaction even in the absence of DTT. Conversely, replacing Ser-80 and Phe-201 in Rt6.2 with cysteines, as in Rt6.1, converted the thiol-independent Rt6.2 NADase to a thiol-dependent enzyme. Kinetic study of the NADase reaction revealed that the affinity of Rt6.1 for NAD and the rate of catalysis increased in the presence of DTT. Moreover, the NADase activity of Rt6.1 expressed on COS-7 cells was stimulated by culture supernatant from activated mouse macrophages, even in the absence of DTT. From these observations, we conclude that t!he Rt6.1 antigen has thiol-dependent NADase activity, and that Cys-80 and Cys-201 confer thiol sensitivity to Rt6.1 NADase. Our results also suggest that upon the interaction of T-cells expressing Rt6.1 with activated macrophages, the NADase activity of the antigen will be stimulated.

ADP Ribose Transferases↗
PubMed2000

Heat-induced cellular damage and tolerance in combination with adriamycin for the PC-3 prostate cancer cell line: relationships with cytotoxicity, reactive oxygen species and heat shock protein 70 expression.

OBJECTIVE: To analyze the relationships among the antitumor effect of chemothermotherapy, generation of reactive oxygen species (ROS), and expression of heat shock protein 70 (HSP-70) in the PC-3 prostate cancer cell line. MATERIALS AND METHODS: Changes in cell proliferation, cell cycle fractions, intracellular ROS accumulation and HSP-70 expression were examined after thermotherapy of PC-3 cells at 41, 42, 43 and 44 degrees C and/or simultaneous treatment with Adriamycin for 1 h, using the trypan blue dye exclusion method, flow cytometry, fluorescent 2', 7'-dichlorofluorescein (DCF) assay, and Western blot analysis. RESULTS: A significant decrease in the number of viable cells was observed with chemothermotherapy compared with thermotherapy at 42, 43, or 44 degrees C (p<0.05). DNA distribution histograms revealed cell accumulation in the S-G(2)/M phase after thermotherapy at 43 degrees C and after chemothermotherapy at 37, 41, 42 and 43 degrees C. After thermotherapy and chemothermotherapy at 44 degrees C, DNA histograms revealed no accumulation of cells with S-G(2)/M DNA content and cells exhibited a marked loss of viability. A significant increase in DCF production was observed with chemothermotherapy compared with thermotherapy at 42, 43 or 44 degrees C (p<0.05, p<0.01 and p<0.01, respectively). HSP-70 levels increased linearly with increasing temperature. HSP-70 levels after thermotherapy and chemothermotherapy increased with time and reached plateaus at 30 min, whereas the level after thermotherapy at 44 degrees C decreased at 60 min. CONCLUSIONS: In conclusion, one possible synergism in cytotoxic effects of chemothermotherapy and Adriamycin could be evaluated by the relationship between ROS accumulation and HSP-70 expression in the PC-3 prostate cancer cell line.

Antineoplastic Agents↗
PubMed2000

Electrophysiologic analysis of antidepressant drug effects on the GABA(A) receptor complex based upon antagonist-induced encephalographic power spectrum changes.

To better understand antidepressant drug effects on the GABA(A) receptor complex (the GABA(A) receptor, chloride ionophore and benzodiazepine receptor), we investigated how antidepressants influenced power spectrum changes induced by pentylenetetrazol (PTZ), a chloride ionophore antagonist, in the rat hippocampal electroencephalogram (EEG). In control recording, PTZ (27.5 mg/kg i. p.) increased EEG power at frequencies under 12 Hz up to five times. After rats were pretreated with imipramine, fluoxetine or trazodone for 7 days (10 mg/kg i.p., twice a day), PTZ could not increase EEG power to more than three times the power before injection; this effect was not observed after pretreatment for 3 days. These three antidepressants inhibit serotonin uptake, while two other antidepressants, desipramine and nortriptyline, that inhibit norepinephrine uptake failed to counter the PTZ effect. We concluded that antidepressants with serotonergic effects enhanced the function of the GABA(A) receptor complex.

Animals↗